WVU doctoral candidate Ashley Brandebura has received an NIH grant to study the calyx of Held, the largest nerve terminal in the brain.

Monday, September 10, 2018

You’re taking a walk, and you hear a dog growl. Is it behind you or in front of you? Two houses down or at your heels? The calyx of Held, which is located in the part of the brain that controls hearing, helps you discern this instantly.

A West Virginia University graduate student is studying how certain cells affect the development of this part of the brain, and therefore, how they could affect how quickly and accurately the brain processes sounds.

The National Institute on Deafness and Other Communication Disorders, a division of the National Institutes of Health, has awarded Ashley Brandebura, a graduate research assistant at WVU’s Rockefeller Neuroscience Institute, $44,000 over two years to study the calyx of Held.

The calyx of Held is the largest nerve terminal in the brain. Its highly specialized function makes it a key player in the brain’s ability to make sense of sounds, in particular, precisely identifying where a sound comes from.

Brandebura is analyzing the role that two types of cells play in the calyx of Held’s growth and the maturation of the brain region where it resides. The first type, neurons, transmit information within the brain and from the brain to other parts of the body. The second type, glial cells, surround neurons to support and insulate them. Taken together, they resemble the wires and insulation that make up an electrical cord.

Brandebura, who is pursuing her biochemistrydoctorate at the WVU School of Medicine, hypothesizes that both neurons and glial cells secrete the key signaling molecules that guide the calyx of Held through its development.

“A lot of people just focus on the neurons and how they fire together, but we’re interested in the glial cells as well,” she said.

The calyx of Held is a large, fast-growing junction that participates in the transmission of sounds from the ear to a part of the brain that specializes in locating the sounds’ sources. Such nerve junctions are called synapses.

“Ashley’s work utilizes state-of-the-art techniques to measure gene expression in individual glial and neuronal cells. It is a so-called ‘big data’ approach to science that requires knowledge of biology, computer programming and statistics,” said George Spirou, who teaches in WVU’s School of Medicine, directs the Otolaryngology Residency Research Program and is Brandebura’s primary mentor. She is co-mentored by Peter Stoilov and Peter Mathers in the Department of Biochemistry.

Defining how neural circuits develop on a molecular scale can help researchers learn about conditions that stem from atypical neural wiring. Understanding how neurons and glial cells “talk” among each other may underpin discoveries in this area.

In particular, Brandebura’s work could shed light on why autistic individuals are often oversensitive—or not sensitive enough—to sounds.

A part of the brain that the calyx of Held connects to, called the medial nucleus of the trapezoid body, tends to be unusually small in people with autism. “It’s disorganized,” explained Brandebura, “and there are some indications that the circuitry is not transmitting properly.

By investigating how neurons and glial cells signal the calyx of Held to grow and the medial nucleus of the trapezoid body to mature, Brandebura may gain a new perspective into the abnormal auditory processing characteristic of autistic individuals.

Her research could also influence how clinicians treat cases of Alzheimer’s disease or stroke, two conditions characterized by synaptic breakdowns.

“If you know how these synapses form in early development,” she said. “You could try to upregulate these early developmental pathways to regenerate brain tissue.”